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DNA topoisomerase II was newly identified as one of autoantigens which were reactive with antinuclear antibodies (ANAs) in patients with primary liver cancer. Another novel autoantigen that was a target of ANA from liver cancer, a 120 kilodalton nucleolar protein, has been characterized. That was shown to be localized in the dense fibrillar region of the nucleolus. Molecular nature of the protein has been currently under investigation with molecular cloning technique.From prospective study with 587 patients with chronic liver disease, six patients showed seroconversion of ANA from negative to positive, changes in ANA titers or ANA specificities. Of these 6 patients, two were diagnosed as having hepatocellular carcinoma, one as having metastatic liver cancer, and one was under interferon therapy for hepatitis C.It was speculated that changes in ANA in patients with chronic liver disease might be associated with development of liver cancer or interferon therapy.In the study of comparison of the spectrum of autoantigens which were targets of antibodies in chronic liver disease patients with or without primary liver cancer, non-muscle myosin was identified as autoantigen in 3 patients exclusively with chronic hepatitis C without liver cancer. On the other hand, antibodies to tumor suppresser gene product, p53, was detected in 2 patients with hepatocellular carcinoma and none in chronic liver disease without cancer. There might be certain difference in the spectrum of autoantigensin chronic liver disease patients with or without liver cancer.